1. Field of the Invention
The present invention provides a process for the enantioselective epoxidation of C.dbd.C double bonds. In particular, the invention relates to the epoxidation of compounds of the general formula I ##STR2##
in which
R.sup.1 and R.sup.2, independently, represent (C.sub.1 -C.sub.18)-alkyl, PA1 (C.sub.2 -C.sub.128)-alkenyl, (C.sub.2 -C.sub.18)-alkynyl, (C.sub.6 -C.sub.18)-aryl, PA1 (C.sub.7 -C.sub.19)-aralkyl, (C.sub.3 -C.sub.18)-heteroaryl, (C.sub.4 -C.sub.19)-heteroaralkyl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.6 -C.sub.18)-aryl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.3 -C.sub.19)-heteroaryl, (C.sub.3 -C.sub.8)-cycloalkyl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.3 -C.sub.8)-cycloalkyl, PA1 (C.sub.3 -C.sub.8)-cycloalkyl-(C.sub.1 -C.sub.8)-alkyl, PA1 R.sup.3 and R.sup.4, independently, represent H, (C.sub.1 -C.sub.18)-alkyl, PA1 (C.sub.2 -C.sub.8)-alkenyl, (C.sub.6 -C.sub.18)-aryl, (C.sub.3 -C.sub.18)-heteroaryl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.6 -C.sub.18)-aryl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.3 -C.sub.19)-heteroaryl, (C.sub.3 -C.sub.8)-cycloalkyl, or PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.3 -C.sub.8)-cycloalkyl, PA1 R.sup.1 and R.sup.2, independently, represent (C.sub.1 -C.sub.18)-alkyl, PA1 (C.sub.2 -C.sub.18)-alkenyl, (C.sub.2 -C.sub.18)-alkynyl, (C.sub.6 -C.sub.18)-aryl, PA1 (C.sub.7 -C.sub.19)-aralkyl, (C.sub.3 -C.sub.18)-heteroaryl, (C.sub.4 -C.sub.19)-heteroaralkyl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.6 -C.sub.18)-aryl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.3 -C.sub.8)-heteroaryl, (C.sub.3 -C.sub.8)-cycloalkyl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.3 -C.sub.8)-cycloalkyl, PA1 (C.sub.3 -C.sub.8)-cycloalkyl-(C.sub.1 -C.sub.8)-alkyl, PA1 R.sup.3 and R.sup.4, independently, represent H, (C.sub.1 -C.sub.18)-alkyl, PA1 (C.sub.2 -C.sub.18)-alkenyl, (C.sub.6 -C.sub.18)-aryl, (C.sub.3 -C.sub.18)-heteroaryl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.6 -C.sub.18)-aryl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.3 -C.sub.19)-heteroaryl, (C.sub.3 -C.sub.8)-cycloalkyl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.3 -C.sub.8)-cycloalkyl, PA1 R.sup.1 represents (C.sub.1 -C.sub.18)-alkyl, (C.sub.2 -C.sub.18)-alkenyl, PA1 (C.sub.6 -C.sub.18)-aryl, (C.sub.3 -C.sub.18)-heteroaryl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.6 -C.sub.18)-aryl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.3 -C.sub.19)-heteroaryl, (C.sub.3 -C.sub.8)-cycloalkyl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.3 -C.sub.8)-cycloalkyl, PA1 R.sup.2 represents (C.sub.1 -C.sub.18)-alkyl, (C.sub.2 -C.sub.18)-alkenyl, PA1 (C.sub.6 -C.sub.18)-aryl, (C.sub.3 -C.sub.18)-heteroaryl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.6 -C.sub.18)-aryl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.3 -C.sub.19)-heteroaryl, (C.sub.3 -C.sub.8)-cycloalkyl, PA1 (C.sub.1 -C.sub.8)-alkyl-(C.sub.3 -C.sub.8)-cycloalkyl, PA1 R.sup.3 and R.sup.4 are defined in the same way as above.
wherein the groups mentioned above may be substituted once or several times with heteroatoms such as a halogen, NR.sup.3 R.sup.4, PO.sub.0-3 R.sup.3 R.sup.4, OR.sup.3, SR.sup.3, SOR.sup.3, SO.sub.2 R.sup.3, SO.sub.3 R.sup.3 or groups such as CO.sub.2 R.sup.3, CONHR.sup.3 and one or more CH.sub.2 groups may be substituted by heteroatoms such as NR.sup.3, PR.sup.3, O or S,
wherein the groups mentioned above may be substituted once or several times with a halogen, by means of a diastereomer and enantiomer enriched homopolyamino acid and an oxidizing agent.
2. Background Information
Enantioselective epoxidation reactions are important reactions for building up chiral intermediates for organic syntheses. In particular, the asymmetric epoxidation of allyl alcohols according to Sharpless et al. and manganese salt promoted enantioselective epoxidation according to Jacobsen et al. are well established in organic syntheses for the building up of chiral molecules (Sharpless et al., J. Am. Chem. Soc. 1980, 102, 5974; J. Am. Chem. Soc. 1987, 109, 5765; J. Org. Chem. 1986, 51, 1922; Jacobsen et al., J. Am. Chem. Soc. 1990, 112, 2801; J. Am. Chem. Soc. 1991, 113, 7063).
Another possibility for the asymmetric epoxidation of C.dbd.C double bonds has been disclosed in the reaction of chalcones with hydrogen peroxide in the presence of enantiomer enriched polyamino acids (Colonna et al., Org. Synth.; Mod. Trends, Proc. IUPAC Symp. 6th, 1986, 275; Julia et al., Angew. Chem., Int. Ed. Engel, 1980, 19, 929).
The methods of synthesis just mentioned all have the disadvantage that they can be applied to a relatively narrow range of substrates. For this reason, and because of the continuing research taking place in this area, there is a need to provide improved epoxidation procedures.
Two different variants of the Julia-Colonna epoxidation reaction, the two phase and the three phase variants, have been disclosed in the prior art to date (S. M. Roberts et al. Chem. Commun. 1998, 1159; WO 96/33183). The two phase variant makes use of an organic solvent and operates with oxidizing agents which are soluble in these solvents, in the presence of insoluble homopolyamino acids. The three phase variant uses water as the third phase, in addition to the water-insoluble organic solvent. Thus, water-soluble oxidizing agents can advantageously be used for the reaction; optionally in the presence of phase transfer catalysts.
From documents relating to the last-mentioned epoxidation reaction, however, it is clear that there are critical defects in this method of epoxidation with regard to its use in an industrial process, these being the occasionally low space/time yield (reaction times of the order of days) and the poor ee-values which are sometimes obtained for many substrates.